{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:32:47Z","timestamp":1791891167741,"version":"4.3.4"},"reference-count":30,"publisher":"Georg Thieme Verlag KG","issue":"04","funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"crossref","award":["17-29084A"],"award-info":[{"award-number":["17-29084A"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Reconstr Microsurg"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background\u2003Lymphedema is a chronic condition characterized by progressive edema with complicated treatment. Recently, new treatment strategies inducing lymphangiogenesis were proposed. The aim of our study was to examine the effect of vascular endothelial growth factor C (VEGF-C) and adipose-derived stem cells (ADSCs) on lymphatic regeneration and drainage re-establishment in vascularized lymph node transfer (VLNT) model using a pedicled vascularized lymph node (VLN) groin flap.<\/jats:p><jats:p>Methods\u2003Female Lewis rats with groin VLN flaps were utilized as a lymphedema model. Group A served as the control. Group B received VEGF-C. Group C received both VEGF-C and ADSCs. Group D received ADSCs only. Lymphatic drainage re-establishment was evaluated by ultrasound\u2013photoacoustic imaging (US-PAI) after indocyanine green (ICG) injection.<\/jats:p><jats:p>Results\u2003The fastest regeneration of elevated flaps was observed in Groups B and C in all monitored periods. After the first month, ICG positivity was detected in 14.3% of animals in Group A, 71.43% of animals in Group B (odds ratio [OR]\u2009=\u200915; p\u2009=\u20090.048), and 83.33% in Group C (OR\u2009=\u200930; p\u2009=\u20090.027). On the contrary, the difference between control group and Group D (16.67%; p\u2009=\u20090.905) was statistically insignificant. Administration of VEGF-C, ADSC\u2009+\u2009VEGF-C, and ADSC led to full flap regeneration after 6 months. The control group had the lowest percentage of ICG positivity at all monitored time points.<\/jats:p><jats:p>Conclusion\u2003We found that the fastest regeneration occurred with the combination of the VLN flap and VEGF-C. The addition of ADSC had an insignificant effect in our study. Furthermore, we proved the feasibility of PAI as an assessment tool of the lymphatic drainage recovery in a VLNT model.<\/jats:p>","DOI":"10.1055\/a-1896-5471","type":"journal-article","created":{"date-parts":[[2022,7,11]],"date-time":"2022-07-11T23:21:35Z","timestamp":1657581695000},"page":"311-319","source":"Crossref","is-referenced-by-count":8,"title":["The Effect of Vascular Endothelial Growth Factor C and Adipose-Derived Stem Cells on Lymphatic Regeneration in a Rat Vascularized Lymph Node Transfer Model"],"prefix":"10.1055","volume":"39","author":[{"given":"Filip","family":"Jonas","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University Hospital Bulovka, First Faculty of Medicine, Charles University, Prague, Czech Republic"},{"name":"Department of Plastic Surgery, Third Faculty of Medicine, Teaching Hospital Kr\u00e1lovsk\u00e9 Vinohrady, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kesa","sequence":"additional","affiliation":[{"name":"Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Paral","sequence":"additional","affiliation":[{"name":"Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Pankrac","sequence":"additional","affiliation":[{"name":"Center for Advanced Preclinical Imaging (CAPI), First Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie Hubalek","family":"Kalbacova","sequence":"additional","affiliation":[{"name":"Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Miletin","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Third Faculty of Medicine, Teaching Hospital Kr\u00e1lovsk\u00e9 Vinohrady, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Sukop","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, Third Faculty of Medicine, Teaching Hospital Kr\u00e1lovsk\u00e9 Vinohrady, Charles University, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Molitor","sequence":"additional","affiliation":[{"name":"Department of Plastic Surgery, University Hospital Bulovka, First Faculty of Medicine, Charles University, Prague, Czech 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Li","year":"2018","journal-title":"Photoacoustics"},{"issue":"02","key":"ref18","doi-asserted-by":"crossref","first-page":"192e","DOI":"10.1097\/01.prs.0000437257.78327.5b","article-title":"The mechanism of vascularized lymph node transfer for lymphedema: natural lymphaticovenous drainage","volume":"133","author":"M-H Cheng","year":"2014","journal-title":"Plast Reconstr Surg"},{"issue":"04","key":"ref19","doi-asserted-by":"crossref","first-page":"503e","DOI":"10.1097\/PRS.0000000000004760","article-title":"Reestablishment of lymphatic drainage after vascularized lymph node transfer in a rat model","volume":"142","author":"M Najjar","year":"2018","journal-title":"Plast Reconstr Surg"},{"issue":"09","key":"ref20","doi-asserted-by":"crossref","first-page":"3668","DOI":"10.1096\/fj.14-268920","article-title":"Angiopoietin-4 increases permeability of blood vessels and promotes lymphatic dilation","volume":"29","author":"C T Kesler","year":"2015","journal-title":"FASEB 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